Case study: COVID-19 vaccine choice and booster timing on ocrelizumab
Case study: COVID-19 vaccine choice and booster timing on ocrelizumab
This case study is about whether or not you need to delay your next ocrelizumab infusion before having your booster COVID-19 vaccine and which vaccine to choose if you can.
Case
I am a 28-year old woman (178 cm tall and weigh 62kg) who has been on ocrelizumab (Ocrevus) for close to three years. I had my fifth course of treatment in April. I have had two doses of the Pfizer-BionTech COVID-19 vaccine three weeks apart in Februrary of this year. I have had an antibody test and have no antibodies to the coronavirus spike protein. Apart from my total lymphocyte count being 0.8/mm3, with no peripheral B-cells (0/mm3), I am otherwise well. I am due for my next course of ocrelizumab in October.
Should I delay the course? I am concerned that my disease may reactivate.
My neurologist has recommended a third dose of the Pfizer-BionTech vaccine now, i.e. at month 5 after my last course, and to go ahead with my next ocrelizumab infusion 4 weeks later.
Considering that I did not seroconvert after the first two doses of the Pfizer-BionTech vaccine would you recommend I change vaccines?
Prof G’s opinion
The advice you have been given is what I call ‘toeing the party line’, which is based on the results of the Roche-Genentech VELOCE vaccine study. The fact that you have no B-cells in your peripheral blood means you are unlikely to make an antibody response with the third or booster dose of the vaccine. This, however, does not mean you don’t have immunity against the SARS-CoV-2 virus. Several groups have shown T-cell responses in vaccinated subjects on anti-CD20 therapies who don’t have antibodies. What I can’t tell you at present is if this T-cell immunity will be sufficient to protect you against COVID-19 and more importantly severe COVID-19. However, because of your age and lack of comorbidities you should be okay if you develop COVID-19. The risk of mortality in pwMS on ocrelizumab as a result of COVID-19 is greater in older subjects (>50 years) and those with other comorbidities.
If you are interested in working out your mortality risk I suggest using Oxford’s online Q-COVID risk calculator, which I completed for you. It does not allow you to tick a box for having MS, so I substituted having rheumatoid arthritis or SLE for MS. You can see that your risk of dying from COVID-19 is about 1 in 170,000, which is low. In reality with some T-cell immunity from your vaccines, this risk will be even lower than this.
Now let’s say you were a male of 55 and were slightly overweight (height 178 and weight of 106kg) the risk of death from COVID-19 would increase to approximately 1 in 8,000. So if you had a higher risk of mortality you may have a different opinion about being seronegative after vaccination.
One factor that is not been taken into account in these calculations is the fact that you are mildly lymphopaenic, which in my experience is quite common in pwMS on anti-CD20 therapy. As you are only mildly lymphopaenic and you are young this is not a concern for me. However, if you were over 50 years of age, because of superimposed immunosenescence, I would be concerned.
So I think the advice your neurologist has given you is reasonable. The alternative choice is for you to miss or delaying your next dose of ocrelizumab and wait until you get some B-cell reconstitution. Based on my interpretation of the literature you need to have at least 10 B-cells per millilitre of blood to be able to mount an antibody response to the COVID-19 vaccines. How quickly you reconstitute is difficult to predict, but as you are small (62kg) this may take 9 months, 12 months or even longer.
If you do miss a dose of ocrelizumab or delay the dose I wouldn’t be too concerned about your MS disease activity returning. In the vast majority of pwMS who go without treatment for up to 18 months after having had 3 or 4 courses of ocrelizumab, their MS remains in remission (see Baker et al. Mult Scler Relat Disord. 2020 Sep;44:102279).
Which vaccine?
It is now clear that antibody titres are the highest after the Moderna RNA-COVID-19 vaccine and immunity lasts the longest with this vaccine with greater protection against severe disease.
A study in the NEJM on the real-world effectiveness of the vaccines in preventing symptomatic illness in about 5,000 health care workers found that the Pfizer-BioNTech vaccine had an effectiveness of 88.8% compared with Moderna’s 96.3%.
The CDC in the US has also found that the efficacy of the Pfizer-BioNTech vaccine against hospitalization fell from 91% to 77% after a four-month period following the second shot, whereas the Moderna vaccine showed no decline over the same period of time.
Based on these data I would suggest going for the Moderna and not the Pfizer-BionTech vaccine. However, if you don’t have a choice the Pfizer-BionTech vaccine will also be fine. Please don’t worry about mixing vaccines, there is no evidence this is a problem and there may be theoretical reasons why this is preferable.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.
A couple of questions Prof.....at the start of the vaccination period your advice was that some immunity was better than none. For a number of ocrelizumab patients, by the time they wait for b-cell repopulation we will be in to next Spring and the winter wave will have hopefully passed. Should these patients grab the chance to boost t-cell responses or not bother? Also, the flu jab invites are beginning to come out. Again, i assume the advice would be to take up this offer but will it really help with no bcells?
This is really helpful. I'm in a similar position in terms of vaccination dates and ocrevus schedules, though a little older at 40. I haven't had an antibody test though, so should probably seek one out.